Dose escalation starting at 20 mg, oral once or twice a day, 28 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.

X-82

Gina Courtney, MD

The purpose of this study is to determine the maximum tolerated dose (MTD) of X-82 as a single agent.

Safety Study of X-82 in Patients With Advanced Solid Tumors

Phase I, First in Human, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of X-82 in Patients With Advanced Solid Tumors

To determine the maximum tolerated dose (MTD) of X-82 as a single agent.

To characterize the preliminary pharmacokinetics (PK) of X-82 given as a single agent.

To explore the preliminary biological activity and clinical tumor response after treatment with X-82 given as a single agent.

Tyrogenex

Symptoms and General Pathology

All Conditions

Neoplasms

Rare Diseases

Recurrence

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

All Drugs and Chemicals

Amino Acids

Nilotinib

Mitogens

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Patients will take nilotinib twice daily at the standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects.

nilotinib

David Piccioni, MD, PhD

The purpose of this study is to determine the survival, disease response, and side effects of Tasigna® (nilotinib) in patients who have malignant gliomas and are positive for Platelet Derived Growth Factor Receptor (PDGFR) amplification. This study is designed to test the hypothesis that patients with malignant gliomas with PDGFR amplification are sensitive to PDGFR kinase inhibitors.

Malignant gliomas (MG), including anaplastic gliomas (AG) and glioblastoma (GBM), are the most common primary brain tumor. Standard of care (surgery, radiotherapy, and temozolomide at initial diagnosis) results in a median survival of only 14 months. For patients with recurrent disease, conventional chemotherapy is generally ineffective with response rates \<20%. Clearly there is need for improved treatments. Recent genome-wide studies have confirmed that GBM is a heterogeneous group of diseases that can be subclassified by shared genetic aberrations. The implication is that, in part, the underlying genetics may determine responsiveness to treatments and thus allow us to personalize therapy.

This is an, open-label, non-randomized, phase II study with oral nilotinib in adult patients with biomarker-enriched, recurrent malignant gliomas who have developed tumor progression after standard therapy. Patients will be treated with oral nilotinib (starting with the labeled dose of 400 mg) daily until disease progression or intolerance. One cycle is defined as 28 days.

Approximately 50 evaluable patients will be enrolled in this study, with 32 (grade IV) and 18 (grade III) in separate arms.

All patients will undergo clinical evaluation after each 28-day cycle. Neuroimaging studies (MRI) will be performed at baseline, 4 weeks, 8 weeks and then after every 2 cycles (8 weeks). If a contraindication for MRI's exists, patients will undergo contrast-enhanced CT scans. Laboratory tests will be obtained weekly during the first 4 weeks, and then on days 1 and 15 of all subsequent cycles. Patients will remain on study medication unless they develop tumor progression or unacceptable toxicity.

Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas

A Phase II Study of PDGFR Kinase Inhibitor in Biomarker-Enriched Recurrent Malignant Gliomas

Progression was defined by McDonald Criteria: A 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, OR clear worsening of any evaluable disease, OR appearance of any new lesion/site, OR clear clinical worsening OR failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer).

How many patients who had decrease in tumor size or complete disappearance of tumor.

Novartis

David Piccioni, M.D., Ph.D

Assistant Clinical Professor

Patients will take nilotinib twice daily at the standard dose of 400mg taken by mouth twice a day until disease progression or development of unacceptable side effects.

nilotinib: 400mg po (orally) BID (twice daily)

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

Lara Rose

38 patients were enrolled, but only 34 were treated

Number of Patients Who Had 6-month Progression-free Survival.

38 patients enrolled, but only 34 received study drug

Overall Response Rate

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Blood and Lymph Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Leukemia

Hematologic Neoplasms

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Gastrointestinal Stromal Tumors

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Head and Neck Neoplasms

Myeloid Leukemia

Acute Myeloid Leukemia

Ovarian Cancer

Ovarian Epithelial Cancer

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Dovitinib (TKI) will be dosed on a flat scale of 500 mg on a 5 days on/2 days off dosing schedule.

Dovitinib (TKI258)

Novartis Pharmaceuticals

The purpose of this signal seeking study was to determine whether treatment with dovitinib (TKI258) demonstrated sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

This was a phase II, open label study to determine the efficacy and safety of treatment with dovitinib (TKI258) in patients with a diagnosis of select solid tumors or hematological malignancies that have been pre-identified (prior to study consent) to have mutations, translocations or amplifications and whose disease has progressed on or after standard treatment.

Genomic profiling is becoming more accessible to patients and their physicians. As such, more patients have been identified with potentially-actionable mutations, translocations or amplifications but do not have access to targeted drug treatment. This is a signal-seeking study to match patients with tumor pathway activations inhibited by dovitinib to the RTK inhibitor dovitinib. Pre-identification of mutations, translocations, or amplifications will be performed locally at a CLIA certified laboratory prior to participation on the trial.

For the purpose of this study, genomic profiling is not considered part of screening. Informed consent must be signed before any screening activities take place. Once eligibility (screening criteria met) has been confirmed by Novartis, the patient will initiate therapy with dovitinib single-agent. The patient may not receive any additional anti-cancer therapy during treatment with dovitinib.

Patients received study treatment until disease progression (assessed by investigator per RECIST 1.1 or appropriate hematologic response criteria), unacceptable toxicity, death or discontinuation from study treatment for any other reason (e.g., withdrawal of consent, start of a new anti-neoplastic therapy or at the discretion of the investigator), otherwise known as End of Treatment. All patients who discontinue from study treatment due to disease progression must have their progression clearly documented.

Disease assessment (by RECIST 1.1 or appropriate hematological response criteria) will be performed every 8 weeks (±4 days) after first dose of study drug (Day 1 of every odd cycle), until disease progression or end of treatment, whichever occurs first. The frequency of disease assessment may be reduced to every 12 weeks for patients who have at least 4 post-baseline disease assessments and are clinically stable (except AML patients). Scans was assessed locally by the investigator. After discontinuation of treatment, patients, regardless of reason for treatment discontinuation, will be followed for safety for 30 days after the last dose.

All patients will be followed for survival status every 3 months for 2 years after the last patient has enrolled in the study,regardless of treatment discontinuation reason (except if consent is withdrawn or patient is lost to follow-up)

Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 2 - Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib Including Tumors With Mutations or Translocations of FGFR, PDGFR, VEGF, cKIT, FLT3, CSFR1, Trk and RET

CBR determined by investigator assessment for each tumor assessment \& defined as responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) ≥ 16 wks. Confirmed CR/PR or SD prior to 16 wks,but discontinued prior to 16 wks for reasons other than progressive disease,will have their clinical benefit defined non-evaluable; confirmed CR/PR or SD prior to 16 wks,but progressed prior to 16 wks,will be considered not achieving clinical benefit;if CR/PR/SD occurred prior to 16 wks,but progressed at or after 16 wks without evidence of CR/PR/SD at or after 16 wks,will also be considered not achieving clinical benefit. CBR will be analyzed by comparing achieved CBR with a historical control rate of each tumor type,\& if there is at least 90% probability that the response rate in a tumor type exceeds the historical rate,then the tumor type will be considered a success. CBR: CR+PR+SD the assessment criteria was RECIST 1.1

Overall Response (OR) of Partial Response (PR) or greater based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria will apply and are included in the appendices. ORR: CR+PR

Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.

Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact

TKI258

Age, Continuous

Study Director

Complete response (CR)

Partial response (PR)

Stable disease (SD)

Clinical benefit rate (CBR)

Full Analysis Set (FAS) included all patients who received at least one dose of study drug.

FAS was used for the analysis of efficacy endpoints.

Clinical Benefit Rate (CBR)

Overall response rate (ORR)

Overall Response (OR) of Partial Response (PR) or Greater

Progression-Free Survival (PFS)

Overall Survival (OS)

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Doxorubicin

Liposomal doxorubicin

Immunoglobulins

Olaratumab

Anti-Bacterial Agents

Antibiotics, Antitubercular

Liposomal Doxorubicin Monotherapy until disease progression. Upon disease progression the participant had the option to receive Olaratumab monotherapy.

20 milligrams per kilogram (mg/kg) administered by intervenous (IV) infusion every 2 weeks (14 days). Treatment will continue until there is evidence of progressive disease (PD) or development of unacceptable toxicity

40 milligrams per square meter (mg/m²) administered according to the manufacture's instructions every 4 weeks (28 days). Treatment will continue until there is evidence of PD or development of unacceptable toxicity

liposomal doxorubicin

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of this study is to determine if participants with platinum-refractory or platinum-resistant advanced ovarian cancer have a better outcome when treated with Olaratumab (IMC-3G3) in combination with Liposomal Doxorubicin than when treated with Liposomal Doxorubicin alone.

The primary objective of this study is to evaluate the progression-free survival (PFS) in participants with platinum-refractory or platinum-resistant advanced ovarian cancer when treated with the monoclonal antibody Olaratumab in combination with liposomal doxorubicin versus liposomal doxorubicin alone.

A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer

Randomized Phase 2 Trial Investigating Liposomal Doxorubicin With or Without Anti-Platelet Derived Growth Factor Receptor-Alpha (PDGFRα) Monoclonal Antibody IMC-3G3 in Patients With Platinum-Refractory or Platinum-Resistant Advanced Ovarian Cancer

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

PFS is defined as the time from the day of randomization to the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0) criteria or death from any cause. Progressive Disease (PD) is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.

OS is defined as the time from first day of therapy to the date of death from any cause. Participants who were alive at the end of the follow-up period or were lost to follow-up, OS was censored on the last date the participant was known to be alive.

The percentage of participants with a best overall response of confirmed CR or PR defined using RECIST v1.0 criteria. CR is the disappearance of all target and non-target lesions and normalization of cancer antigen-125 (CA-125) levels. PR is defined as having a ≥30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. The percentage of participants with objective response was calculated as: (number of participants whose best overall response of CR or PR/number of participants treated) \* 100.

Duration of response is the interval from the date of initial CR or PR until the first date criteria for PD is met using RECIST v1.0 criteria, or initiation of other (or additional) antitumor therapy is first reported, or death due to any cause. CR is the disappearance of all target and non-target lesions and the normalization of tumor marker levels. PR is a ≥30% decrease in the sum of the LD of target lesions without new lesions and progression of non-target lesions. PD is a ≥20% increase in the sum of the LD of target lesions and/or unequivocal progression of existing non-target lesions and/or detection of 1 or more new lesions. Participants who did not relapse were censored on the day of their last tumor assessment.

Reported are the number of participants with clinically significant events, defined as serious AEs (SAEs) and other non-serious AEs regardless of causality and those who died during treatment and during the 30-day post-dose follow-up. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module of this report.

Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20.

PFS is defined as the time from start of Olaratumab monotherapy to the first evidence of progression as defined by RECIST v1.0 criteria or death from any cause. PD is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a reported prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment.

The time it takes to reduce the concentration of Olaratumab in the plasma by 50%.

CL is the volume of serum cleared of Olaratumab per unit of time after a single dose of Olaratumab

Vss is an estimate of drug distribution independent of the elimination process and is proportional to the amount of drug in the body versus the drug plasma concentration at steady-state.

PFS is defined as the time from the day of randomization to the first evidence of progression as defined by RECIST v1.0 criteria or death from any cause. PD is a 20% increase over the smallest sum of target lesions or new lesions. Participants who died without a prior disease progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of last tumor assessment. PDGFRα protein expression at baseline in tumor cells is determined by IHC using H-Scores and a cut point of 0. Participants were considered to have a high relative expression when H-Score is \>0 and a low relative expression when H-Score=0. H-Score was calculated by summing the percentage of cell staining at each intensity multiplied by the weighted intensity of staining. Staining intensity: 0 (no staining), 1+ (weak staining), 2+ (medium staining), 3+ (strongest staining). H-Scores could range from 0-300.

Eli Lilly and Company

20 mg/kg of Olaratumab was administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days) until there was evidence of PD or development of unacceptable toxicity.

Olaratumab and Liposomal Doxorubicin

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Upon disease progression the participant had the option to receive Olaratumab monotherapy.

Liposomal Doxorubicin

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity followed by 20 mg/kg of Olaratumab administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Liposomal Doxorubicin: Optional Olaratumab Monotherapy

Total

Ethnicity (NIH/OMB)

Asian

Black or African American

Native Hawaiian of Other Pacific Islander

White

Other

Race/Ethnicity, Customized

United States

United Kingdom

Spain

Region of Enrollment

0-Fully Active

1-ambulatory, able to do light/sedentary nature

ECOG PS classified participants according to their functional impairment.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Platinum Refractory

Platinum Resistant

Participants reaction to prior platinum treatment.

Stratification Factor

Modified Intent to Treat (mITT) Population: All participants who were randomized and received any quantity of study drug.

Chief Medical Officer

Modified Intent to Treat (mITT) Population: All randomized participants who received any amount of study drug. Participants censored: Olaratumab=13, Liposomal Doxorubicin=14.

mITT Population: All randomized participants who received any amount of study drug. Participants censored: Olaratumab=21, Liposomal Doxorubicin=23.

mITT Population: All randomized participants who received any amount of study drug.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

All participants who achieved CR or PR. Participants censored: Olaratumab=2, Liposomal Doxorubicin=4.

Median Duration of Response

SAEs

Other Non-SAEs

Deaths on treatment or within 30 days of last dose

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Upon disease progression the participant had the option to receive Olaratumab monotherapy..

All randomized participants who received any amount of study drug.

Number of Participants With Adverse Events (AEs) and Who Died

All randomized participants who received at least one dose of study drug and had evaluable baseline and evaluable post-baseline antibody data.

Percentage of Participants With Anti-Olaratumab Antibodies

Participants who received Olaratumab treatment after PD on liposomal doxorubicin monotherapy. Participants censored=4

PFS of Participants Who Received Olaratumab After Liposomal Doxorubicin Monotherapy (Descriptive Statistics for Safety and Efficacy for Participants Who Continue on Olaratumab Monotherapy Following Disease Progression on Liposomal Doxorubicin Monotherapy)

Zero participants were analyzed. An insufficient amount of samples were collected to derive this measure.

Area Under the Curve (AUC) of Olaratumab

Maximum Concentration (Cmax) of Olaratumab

Half-life (t1/2) of Olaratumab

Clearance (CL) of Olaratumab

40 mg/m² of liposomal doxorubicin was administered according to the manufacturer's instructions every 4 weeks (28 days). Treatment continued until there was evidence of PD or development Olaratumab administered as an IV infusion every 2 weeks (14 days) until there was evidence of PD or development of unacceptable toxicity up to 130 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety Study of X-82 in Patients With Advanced Solid Tumors	NCT01296581	Advanced Solid ...	X-82	18 Years -	Tyrogenex
Study of Platelet Derived Growth Factor Receptor (PDGFR) in Recurrent Malignant Gliomas	NCT01140568	Glioma	nilotinib	18 Years -	University of California, San Diego
Dovitinib for Patients With Tumor Pathway Activations Inhibited by Dovitinib	NCT01831726	Tumor Pathway A...	Dovitinib (TKI2...	18 Years - 100 Years	Novartis
A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer	NCT00913835	Ovarian Neoplas...	Olaratumab liposomal doxor...	18 Years -	Eli Lilly and Company
A Study of Paclitaxel/Carboplatin With or Without Olaratumab (IMC-3G3) in Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)	NCT00918203	Non-Small Cell ...	Olaratumab Paclitaxel Carboplatin	18 Years -	Eli Lilly and Company
Safety Study of X-82 in Patients With Advanced Solid Tumors	NCT01296581	Advanced Solid ...	X-82	18 Years -	Tyrogenex
Open-label Trial of Imatinib Mesylate in Patients With Unresectable Recurrent Glioblastoma Multiforme Expressing PDGFR (Platelet Derived Growth Factor Receptors)	NCT00171938	Glioblastoma	imatinib mesyla...	18 Years -	Novartis
Efficacy and Safety of Imatinib in Chordoma	NCT00150072	Chordoma	imatinib	-	Novartis
Open-label Trial of Imatinib Mesylate in Patients With Unresectable Recurrent Glioblastoma Multiforme Expressing PDGFR (Platelet Derived Growth Factor Receptors)	NCT00171938	Glioblastoma	imatinib mesyla...	18 Years -	Novartis
Safety Study of X-82 in Patients With Advanced Solid Tumors	NCT01296581	Advanced Solid ...	X-82	18 Years -	Tyrogenex
Efficacy and Safety of Imatinib in Chordoma	NCT00150072	Chordoma	imatinib	-	Novartis
A Study of Liposomal Doxorubicin With or Without Olaratumab (IMC-3G3) in Platinum-Refractory or Resistant Advanced Ovarian Cancer	NCT00913835	Ovarian Neoplas...	Olaratumab liposomal doxor...	18 Years -	Eli Lilly and Company
Lucitanib (E3810) in Patients With Advanced Cancer and FGFR, VEGFR, or PDGFR Pathway Aberrations	NCT02747797	Advanced Cancer	Lucitanib	18 Years -	University of California, San Diego
Open-label Trial of Imatinib Mesylate in Patients With Unresectable Recurrent Glioblastoma Multiforme Expressing PDGFR (Platelet Derived Growth Factor Receptors)	NCT00171938	Glioblastoma	imatinib mesyla...	18 Years -	Novartis

Spots Global Cancer Trial Database for pdgfr

Every month we try and update this database with for pdgfr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pdgfr

Every month we try and update this database with for pdgfr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pdgfr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.